Cariporide is a selective sodium-hydrogen antiporter inhibitor patented by a pharmaceutical company Hoechst A.-G. for treatment myocardial ischemia-reperfusion injury. The sodium-hydrogen exchanger is an important player in the pathophysiology of myocardial ischemia-reperfusion injury. The accumulation of hydrogen ions in the myocyte cytosol; during ischemia creates a proton gradient that promotes the efflux of hydrogen ions in exchange for the influx of sodium ions. This sodium buildup can secondary activates the sodium-calcium exchanger to operate in the reverse mode, resulting in a net calcium accumulation in myocyte cytosol, which leads to dysfunction and cell death. By inhibiting sodium-hydrogen exchange, Cariporide can prevent the accumulation of calcium in the cytosol, therefore reduce the infarct size. In clinical trials, Cariporide shows a statistically significant decline in myocardial infarction but increases mortality. Due to the increase in mortality, cariporide did not pass clinical trials.

Lometrexol, formerly known as DDATHF; LY 264618; T-64 was the first glycinamide ribonucleotide formyl transferase (GARFT) inhibitor to be investigated clinically. Lometrexol had been in phase II clinical trial for the treatment non-small cell lung cancer (NSCLC). However, the studies have been discontinued by Tularik Inc, because Company had suggested, that drug would face competition from other companies in the indication

Mazapertine (RWJ-37796) is an arylpiperazine antipsychotic with high affinity to dopamine D2 and D3, serotonin 5-HT1A and alpha 1A-adrenergic receptors. It was being studied in the treatment of schizophrenia.

Darexaban (YM150) is a direct inhibitor of coagulation factor Xa (FXa), discovered by Astellas Pharmaceuticals. FXa is a crucial serine protease in the coagulation cascade, responsible for the cleavage of prothrombin to its active form thrombin, which then converts soluble fibrinogen to insoluble fibrin, activates platelets and causes a formation of a blood clot. Darexaban inhibits factor Xa with a Ki value of 31 nM and shows anticoagulant activity in human plasma. In venous and A-V shunt thrombosis models in rats, darexaban strongly suppressed thrombus formation without affecting bleeding time. Darexaban was investigated in a number of clinical trials for prevention of venous thromboembolism in patients undergoing surgery, prevention of ischaemic events in acute coronary syndrome, prophylaxis of stroke in atrial fibrillation. In 2011 Astellas announced the discontinuation of darexaban because of high competition on anti-FXa drugs market.

Celivarone is a benzofuran derivative with a multifactorial mode of action including class IV Vaughan Williams’ electrophysiological as well as anti-adrenergic properties. It has no iodine and has a limited tissue accumulation compared with amiodarone. Celivarone exhibits effective anti-arrhythmic properties in several ventricular ischemia- or reperfusioninduced arrhythmia models as well as in in vitro and in vivo atrial fibrillation (AF) models. Its electrophysiological properties are similar to amiodarone (multifactorial mode of action) but with different relative effects on the ion channels. At the ventricular level, celivarone shows anti-arrhythmic activities by suppressing reperfusion-induced arrhythmias (i.v. and oral routes) and reducing the early mortality due to myocardial infarction (oral route) in rats models. At the atrial level, celivarone is effective in atrial fibrillation models with restoration of sinus rhythm or prevention of AF induction and AF recurrence.

Tallimustine (also known as FCE 24517), an alkylating benzoyl mustard derivative of distamycin A that was studied as an anti-tumor agent. Tallimustine participated in phase I clinical trial in patients with advanced cancer. As a result, the was obtained the recommended Phase II dosage for tallimustine. However, the further development of this drug was discontinued.

Otamixaban is a synthetically derived parenteral fXa inhibitor currently in late stage clinical development at Sanofi-Aventis for the management of acute coronary syndrome. Otamixaban is a potent (Ki = 0.5 nM), selective, rapid acting, competitive and reversible fXa inhibitor that effectively inhibits both free and prothrombinase-bound fXa. Factor Xa (fXa) is a critical serine protease situated at the confluence of the intrinsic and extrinsic pathways of the blood coagulation cascade. FXa catalyzes the conversion of prothrombin to thrombin via the prothrombinase complex. Its singular role in thrombin generation, coupled with its potentiating effects on clot formation render it an attractive target for therapeutic intervention. In vivo experiments have demonstrated that Otamixaban is highly efficacious in rodent, canine and porcine models of thrombosis. In addition, recent clinical findings indicate that Otamixaban is efficacious, safe and well tolerated in humans and therefore has considerable potential for the treatment of acute coronary syndrome. Following the results of the Treatment of non-ST elevation Acute coronary syndrome with otamixaban, Sanofi has decided to discontinue the investigational programme with otamixaban, due to efficacy lower than expected. Otamixaban did not show superior benefit/risk to the combination of unfractionated heparin.

KETOTREXATE is an antifolate developed to overcome methotrexate (MTX) resistance. However, it demonstrated such potential only in MTX-resistant sensitive L1210/FR8 leukemia cells and its clinical development was discontinued. Unlike MTX, KETOTREXATE exhibited minimal inhibition of purified dihydrofolate reductase, which implies that it does not act as a classical antifolate.

Diflumidone is a non-steroidal antiinflammatory drug. It inhibits the biosynthesis of prostaglandin by bovine seminal vesicle microsomes and arachidonic acid-induced aggregation of human platelets in a concentration-dependent manner. Diflumidone is a competitive inhibitor of prostaglandin synthetase. Diflumidone also inhibits equally the formation of PGE2 and PGF2a, which suggests blockade of endoperoxide formation. The relative topical efficacy of indomethacin and diflumidone for the suppression of ultraviolet-light-induced erythema has been compared in a randomized, double-blind, placebo-controlled study in man. At 24 h after application, the indomethacin-treated sites had significantly less erythema than did the diflumidone-treated sites.

Iodohippuric acid I-125 (I-I25 Hippuran) is radioisotope that was used as a renogram probe in nefhrography in 1960s-1970s. It is an analog of I-131 labeled I(131) hippuran which has been recognized as the radiopharmaceutical standard for the measurement of effective renal plasma flow in subjects with renal failure but which use has been compromised by the suboptimal imaging characteristics of the 364-keV photon of 131I and the delivery of relatively high radiation doses to kidneys and thyroid in patients with impaired renal function. It was shown that radiation risk was rendered to a minimum with the use of the "cocktail" of 169U-EDTA and 125I-hippuran.